Identification

Name
Pivmecillinam
Accession Number
DB01605
Type
Small Molecule
Groups
Approved
Description

Pivmecillinam is a mecillinam prodrug, a pivaloyloxymethyl ester of amdinocillin that is well absorbed orally, but broken down to amdinocillin in the intestinal mucosa. It is active against gram-negative organisms and used as for amdinocillin. [PubChem]

Structure
Thumb
Synonyms
  • Amdinocillin pivoxil
  • amdinocillin, pivaloyloxymethyl ester
  • Pivmecilinamo
  • Pivmecillinamum
External IDs
RO 10-9071
Product Ingredients
IngredientUNIICASInChI Key
Pivmecillinam hydrochloride48FX7N21H232887-03-9UHPXMYLONAGUPC-WKLLBTDKSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SelexidTablet400 mgOralLeo PharmaNot applicableNot applicableCanada
SelexidTablet200 mgOralLeo PharmaNot applicableNot applicableCanada
Selexid Tab 185mgTablet185 mgOralLeo Pharma1985-12-312012-08-02Canada
International/Other Brands
Coactabs / Selexid
Categories
UNII
1WAM1OQ30B
CAS number
32886-97-8
Weight
Average: 439.569
Monoisotopic: 439.214091871
Chemical Formula
C21H33N3O5S
InChI Key
NPGNOVNWUSPMDP-HLLBOEOZSA-N
InChI
InChI=1S/C21H33N3O5S/c1-20(2,3)19(27)29-13-28-18(26)15-21(4,5)30-17-14(16(25)24(15)17)22-12-23-10-8-6-7-9-11-23/h12,14-15,17H,6-11,13H2,1-5H3/t14-,15+,17-/m1/s1
IUPAC Name
[(2S,5R,6R)-6-[(azepan-1-ylmethylidene)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carbonyloxy]methyl 2,2-dimethylpropanoate
SMILES
[H]C(=N[C@@H]1C(=O)N2[C@@H](C(=O)OCOC(=O)C(C)(C)C)C(C)(C)S[C@]12[H])N1CCCCCC1

Pharmacology

Indication

Used to treat infections due to mecillinam-sensitive organisms such as urinary tract infections, salmonellosis and typhoid fever.

Associated Conditions
Pharmacodynamics

Pivmecillinam is a pivaloyloxymethyl ester of amdinocillin that is well absorbed orally, but broken down to amdinocillin in the intestinal mucosa. It is active against gram-negative organisms and used as for amdinocillin.

Mechanism of action

Pivmecillinam interferes with the biosynthesis of the bacterial cell wall however its activity is slightly different from that of other penicillins and cephalosporins

TargetActionsOrganism
APenicillin-binding protein 1A
inhibitor
Clostridium perfringens (strain 13 / Type A)
Absorption

Well absorbed following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinPivmecillinam may increase the anticoagulant activities of (R)-warfarin.
(S)-WarfarinPivmecillinam may increase the anticoagulant activities of (S)-Warfarin.
4-hydroxycoumarinPivmecillinam may increase the anticoagulant activities of 4-hydroxycoumarin.
AcemetacinAcemetacin may decrease the excretion rate of Pivmecillinam which could result in a higher serum level.
AcenocoumarolPivmecillinam may increase the anticoagulant activities of Acenocoumarol.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Pivmecillinam.
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Pivmecillinam.
Anthrax immune globulin humanThe therapeutic efficacy of Anthrax immune globulin human can be decreased when used in combination with Pivmecillinam.
Anthrax vaccineThe therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Pivmecillinam.
ApramycinThe serum concentration of Apramycin can be decreased when it is combined with Pivmecillinam.
Food Interactions
  • Take without regard to meals.

References

General References
  1. Sjovall J, Huitfeldt B, Magni L, Nord CE: Effect of beta-lactam prodrugs on human intestinal microflora. Scand J Infect Dis Suppl. 1986;49:73-84. [PubMed:3547627]
  2. Graninger W: Pivmecillinam--therapy of choice for lower urinary tract infection. Int J Antimicrob Agents. 2003 Oct;22 Suppl 2:73-8. [PubMed:14527775]
  3. Authors unspecified: Pivmecillinam (selexid). Drug Ther Bull. 1978 Dec 22;16(26):103-4. [PubMed:214285]
External Links
Human Metabolome Database
HMDB0015543
KEGG Drug
D02889
PubChem Compound
115163
PubChem Substance
46506880
ChemSpider
16735658
ChEBI
51210
ChEMBL
CHEMBL1616433
Therapeutic Targets Database
DAP001174
PharmGKB
PA164750167
Wikipedia
Pivmecillinam
ATC Codes
J01CR50 — Combinations of penicillinsJ01CA08 — Pivmecillinam
AHFS Codes
  • 08:12.16 — Penicillins

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2TerminatedTreatmentChlamydia Trachomatis Infection / Chlamydial Urethritis1
4CompletedTreatmentAcute Cystitis (Excl in Pregnancy)1
4RecruitingTreatmentPyelonephritis / Urinary Tract Infections (UTIs)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral200 mg
TabletOral400 mg
TabletOral185 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)119 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.0526 mg/mLALOGPS
logP3.23ALOGPS
logP2.91ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)13.66ChemAxon
pKa (Strongest Basic)7.91ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area88.51 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity113.03 m3·mol-1ChemAxon
Polarizability47.7 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.962
Blood Brain Barrier-0.9659
Caco-2 permeable-0.5577
P-glycoprotein substrateSubstrate0.7368
P-glycoprotein inhibitor IInhibitor0.603
P-glycoprotein inhibitor IINon-inhibitor0.5211
Renal organic cation transporterNon-inhibitor0.7087
CYP450 2C9 substrateNon-substrate0.8243
CYP450 2D6 substrateNon-substrate0.8069
CYP450 3A4 substrateSubstrate0.5997
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9396
Ames testNon AMES toxic0.6178
CarcinogenicityNon-carcinogens0.8141
BiodegradationNot ready biodegradable0.5067
Rat acute toxicity2.1874 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9925
hERG inhibition (predictor II)Non-inhibitor0.6363
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acid esters
Alternative Parents
Penams / Acylals / Azepanes / Dicarboxylic acids and derivatives / Thiazolidines / Tertiary carboxylic acid amides / Azetidines / Formamidines / Dialkylthioethers / Carboximidamides
show 9 more
Substituents
Alpha-amino acid ester / Penam / Azepane / Acylal / Dicarboxylic acid or derivatives / Beta-lactam / Tertiary carboxylic acid amide / Thiazolidine / Azetidine / Carboxamide group
show 23 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
penicillanic acid ester, penicillin (CHEBI:51210)

Targets

Kind
Protein
Organism
Clostridium perfringens (strain 13 / Type A)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transferase activity, transferring glycosyl groups
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
pbpA
Uniprot ID
Q8XJ01
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
75176.35 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Graninger W: Pivmecillinam--therapy of choice for lower urinary tract infection. Int J Antimicrob Agents. 2003 Oct;22 Suppl 2:73-8. [PubMed:14527775]

Drug created on August 29, 2007 12:48 / Updated on November 12, 2018 07:30